We will investigate the role of carbonic anhydrase (CA) in the regulation and maturation of urinary acidification and its adaptation to metabolic and respiratory acidosis. First, in cultured cells obtained from inner medullary collecting ducts (IMCD) of either adult or immature rats, we will test the effect of acid loading on the rates of H+ pumping activity and of Cl-/ HCO3 exchange, on carbonic anhydrase (CA) activity and CA messenger RNA (mRNA). Second, we will test in rabbits the response to acid loading of CA activity in cortex, outer medulla and inner medulla and compare that activity to levels of mRNA for CA, band 3 and H+ ATPase. These experiments will reconcile changes in acid-base transport in the kidney with those in mRNA levels. We will compare these responses in vitro and in vivo in immature animals with those in adult animals. These studies will help us to understand why low birth weight infants are more susceptible to acidosis than are adults.